About Clinical Trials

Understanding Clinical Research Studies

Clinical trials are part of clinical research and at the heart of all medical advances. Clinical trials look at new ways to prevent, detect, or treat disease. Studies might involve new investigational
drugs or new combinations of drugs, new surgical procedures or devices, or new ways to use existing treatments. The goal of clinical trials is to determine if a new test or treatment works and is safe. Clinical trials can also look at other aspects of care, such as improving the quality of life for people with chronic illnesses.

People participate in clinical trials for a variety of reasons. Healthy volunteers say they participate to help others and to contribute to moving science forward. Participants with an illness or disease also participate to help others, but also to possibly receive the investigational medication and to have the additional care and attention from the clinical trial staff. Clinical trials offer hope for many people and an opportunity to help researchers find better treatments for others in the future.

Clinical research is medical research that involves people like you. People volunteer to participate in carefully conducted investigations that ultimately uncover better ways to treat, prevent, diagnose, and understand human disease. Clinical research includes trials that test new investigational drugs and therapies as well as long–term natural history studies, which provide valuable information about how disease and health progress.

The idea

The idea for a clinical research study—also known as a clinical trial—often originates in the laboratory. After researchers test new therapies or procedures in the laboratory and in animal studies, the most promising experimental drugs are moved into clinical trials, which are conducted in phases. During a trial, more information is gained about an experimental drug, its risks, and its effectiveness.

The protocol

Clinical research is conducted according to a plan known as a protocol. The protocol is carefully designed to safeguard the participants’ health and answer specific research questions. A protocol describes the following:

Who is eligible to participate in the trial

Details about tests, procedures, medications, and dosages

The length of the study and what information will be gathered

A clinical study is led by a principal investigator (PI), who is often a doctor. Members of the research team regularly monitor the participants’ health to determine the study’s safety and effectiveness.

Protocol review

Each clinical trial in the United States must be approved and monitored by an Institutional Review Board (IRB) to ensure that the risks are minimal and are worth any potential benefits. An IRB is an independent committee that consists of physicians, statisticians, and members of the community who ensure that clinical trials are ethical and that the rights of participants are protected. Federal regulation requires all institutions in the United States that conduct or support biomedical research involving people to have an IRB initially approve and periodically review the research.

Sponsors

Clinical trials are sponsored or funded by various organizations or individuals, including physicians, foundations, medical institutions, voluntary groups, and pharmaceutical companies, as well as federal agencies such as the National Institutes of Health and the Department of Veterans Affairs.

Informed consent

Informed consent is the process of providing potential participants with the key facts about a clinical trial before they decide whether to participate. The process of informed consent (providing additional information) continues throughout the study. To help someone decide whether or not to participate, members of the research team explain the details of the study. Translation or interpretive assistance can be provided for participants with limited English proficiency. The research team provides an informed consent document that includes details about the study, such as its purpose, duration, required procedures, and who to contact for further information. The informed consent document also explains risks and potential benefits. The participant then decides whether to sign the document. Informed consent is not a contract. Volunteers are free to withdraw from the study completely or to refuse particular treatments or tests at any time. Sometimes, however, this will make them ineligible to continue the study.

Types of clinical trials

There are different types of clinical trials.

Natural history studies provide valuable information about how disease and health progress.

Prevention trials look for better ways to prevent a disease in people who have never had the disease or to prevent the disease from returning. Better approaches may include medicines, vaccines, or lifestyle changes, among other things.

Screening trials test the best way to detect certain diseases or health conditions.

Treatments trials test new investigational drugs, new combinations of drugs, or new approaches to surgery or radiation therapy.

Quality of life trials (or supportive care trials) explore and measure ways to improve the comfort and quality of life of people with a chronic illness.

Phases of clinical trials

Clinical trials are conducted in “phases.” Each phase has a different purpose and helps researchers answer different questions.

Phase I trials: Researchers test an experimental drug in a small group of people (20–80) for the first time. The purpose is to evaluate its safety and identify side effects.

Phase II trials: The experimental drug is administered to a larger group of people (100–300) to determine its effectiveness and to further evaluate its safety.

Phase III trials: The experimental drug is administered to large groups of people (1,000–3,000) to confirm its effectiveness, monitor side effects, compare it with standard or equivalent drugs, and collect information that will allow the experimental drug to be used safely.

Phase IV trials: After a drug is approved by the FDA and made available to the public, researchers track its safety, seeking more information about a drug or treatment’s risks, benefits, and optimal use.

Some concepts to understand

Typically, clinical trials compare a new product or therapy with another that already exists to determine if the new one is as successful as, or better than, the existing one. In some studies, participants may be assigned to receive a placebo (an inactive product that resembles the test product, but without its treatment value).

Comparing a new product with a placebo can be the fastest and most reliable way to demonstrate the new product’s therapeutic effectiveness. However, placebos are not used if a patient would be put at risk—particularly in the study of treatments for serious illnesses—by not having effective therapy. Most of these studies compare new products with an approved therapy. Potential participants are told if placebos will be used in the study before they enter a trial.

Randomization is the process by which two or more alternative treatments are assigned to volunteers by chance rather than by choice. This is done to avoid any bias with investigators assigning volunteers to one group or another. The results of each treatment are compared at specific points during a trial, which may last for years. When one treatment is found superior, the trial is stopped so that the fewest volunteers receive the less beneficial treatment.

In single-or double-blind studies, also called single- or double-masked studies, the participants do not know which medicine is being used, so they can describe what happens without bias. "Blind" (or "masked") studies are designed to prevent members of the research team or study participants from influencing the results. This allows scientifically accurate conclusions. In single-blind ("single-masked") studies, only the patient is not told what is being administered. In a double-blind study, only the pharmacist knows; members of the research team are not told which patients are getting which medication, so that their observations will not be biased. If medically necessary, however, it is always possible to find out what the patient is taking.

Many different types of people participate in clinical trials. Some are healthy, while others may have illnesses. A healthy volunteer is a person with no known significant health problems who participates in clinical research to test a new drug, device, or intervention. Research procedures with healthy volunteers are designed to develop new knowledge, not to provide direct benefit to study participants. Healthy volunteers have always played an important role in research.

Healthy volunteers are needed for several reasons. When developing a new technique, such as a blood test or imaging device, healthy volunteers (formerly called "normal volunteers") help define the limits of "normal." These volunteers serve as controls for patient groups and are often matched to patients on characteristics such as age, gender, or family relationship. They receive the same test, procedure, or drug the patient group receives. Investigators learn about the disease process by comparing the patient group to the healthy volunteers.

Factors like how much of your time is needed, discomfort you may feel, or risk involved depends on the trial. While some require minimal amounts of time and effort, other studies may require a major commitment in time and effort on behalf of the volunteer, and may involve some discomfort. The research procedure may also carry some risk. The consent process for healthy volunteers includes a detailed discussion of the study's procedures and tests.

A patient volunteer has a known health problem and participates in research to better understand, diagnose, treat, or cure that disease or condition for others in the future. Research procedures with a patient volunteer help develop new knowledge. These procedures may or may not benefit the study participants.

Patient volunteers may be involved in studies similar to those in which healthy volunteers participate. These studies involve drugs, devices, or interventions that are being studied to determine whether or not they can prevent, treat, or cure disease. The main aim is to prove, by scientific means, the effects and limitations of the experimental drug or device. Consequently, some patients serve as controls by not taking the investigational drug, or by receiving test doses of the drug large enough only to show that it is present, but not at a level that can treat the condition. A study's benefits may be indirect for the volunteers but may help others.

All clinical trials have guidelines about who can participate, called Inclusion/Exclusion Criteria. Factors that allow someone to participate in a clinical trial are "inclusion criteria." Those that exclude or not allow participation are "exclusion criteria." These criteria are based on factors such as age, gender, the type and stage of a disease, previous treatment history, and other medical conditions. Before joining a clinical trial, a participant must qualify for the study. Some research studies seek participants with illnesses or conditions to be studied in the clinical trial, while others need healthy volunteers.
Some studies need both types. Inclusion and exclusion criteria are not used to reject people personally; rather, the criteria are used to identify appropriate participants and keep them safe, and to help ensure that researchers can find new information they need.

Risks and benefits

Clinical trials involve risks, just as routine medical care and the activities of daily living. When weighing the risks of research, you can consider two important factors:

the degree of harm that could result from participating in the study, and

the chance of any harm occurring.

Most clinical studies pose the risk of minor discomfort, which lasts only a short time. However, some study participants experience complications that require medical attention. In rare cases, participants have been seriously injured or have died of complications resulting from their participation in trials of experimental therapies. The specific risks associated with a research protocol are described in detail in the informed consent document, which participants are asked to sign before participating in research. Also, a member of the research team explains the major risks of participating in a study and will answer any questions you have about the study. Before deciding to participate, carefully consider possible risks and benefits.

Potential benefits

Well-designed and well-executed clinical trials provide the best approach for participants to:

Gain access to new investigational drugs or devices before they are widely available.

Receive regular and careful medical attention from a research team that includes doctors and other health professionals.

Help others by contributing to medical research.

Potential risks

Risks to participating in clinical trials include the following:

There may be unpleasant, serious, or even life-threatening side effects to experimental drugs or devices.

The study may require more time and attention than standard treatment would, including visits to the study site, more blood tests, more treatments, hospital stays, or complex dosage requirements.

If you are offered a clinical trial, feel free to ask any questions or bring up any issues concerning the trial at any time. The following suggestions may give you some ideas as you think about your own questions.

The study

What is the purpose of the study?

Why do researchers think the approach may be effective?

Who will fund the study?

Who has reviewed and approved the study?

How are study results and safety of participants being checked?

How long will the study last?

What will my responsibilities be if I participate?

Possible risks and benefits

What are my possible short-term benefits?

What are my possible long-term benefits?

What are my short-term risks, such as side effects?

What are my possible long-term risks?

What other options do people with my disease have?

How do the possible risks and benefits of this trial compare with those options?

Participation and study-related care

What kinds of investigational drugs or devices, procedures and /or tests will I have during the trial?

Will they hurt, and if so, for how long?

How do the tests in the study compare with those I would have outside of the trial?

Will I be able to take my regular medications while in the clinical trial?

Where will I have my medical care?

Who will be in charge of my care?

Personal issues

How could being in this study affect my daily life?

Can I talk to other people in the study?

Cost issues

Will I have to pay for any part of the trial such as tests or the study drug?

If so, what will the charges likely be?

What is my health insurance likely to cover?

Who can help answer any questions from my insurance company or health plan?

Will there be any travel or child care costs that I need to consider while I am in the trial?

Tips for asking your doctor about trials

Consider taking a family member or friend along, for support and for help in asking questions or recording answers.

Plan ahead what to ask — but don't hesitate to ask any new questions you think of while you're there.

Write down your questions in advance, to make sure you remember to ask them all.

Write down the answers, so that you can review them whenever you want.

Ask about bringing a tape recorder to make a taped record of what's said (even if you write down answers).

Ethical guidelines

The goal of clinical research is to develop knowledge that improves human health or increases understanding of human biology. People who participate in clinical research make it possible for this to occur. The path to finding out if a new drug is safe or effective is to test it on patient volunteers. By placing some people at risk of harm for the good of others, clinical research has the potential to exploit patient volunteers. The purpose of ethical guidelines is both to protect patient volunteers and to preserve the integrity of the science. Ethical guidelines in place today were primarily a response to past research abuses.

Informed consent

Informed consent is the process of learning the key facts about a clinical trial before deciding whether to participate. The process of providing information to participants continues throughout the study. To help someone decide whether to participate, members of the research team explain details of the study. The research team provides an informed consent document, which includes such details about the study as its purpose, duration, required procedures, and who to contact for various purposes. The informed consent document also explains risks and potential benefits.

If the participant decides to enroll in the trial, the informed consent document will be signed. Informed consent is not a contract. Volunteers are free to withdraw from the study at any time.

IRB review

Each clinical trial in the United States must be approved and monitored by an Institutional Review Board (IRB) to ensure that the risks are minimal and are worth any potential benefits. An IRB is an independent committee that consists of physicians, statisticians, and members of the community who ensure that clinical trials are ethical and that the rights of participants are protected. Federal regulation requires all institutions in the United States that conduct or support biomedical research involving people to have an IRB initially approve and periodically review the research.

After a clinical trial is completed, the researchers carefully examine information collected during the study before making decisions about the meaning of the findings and about further testing. After a phase I or II trial, the researchers decide whether to move on to the next phase or to stop testing the investigational drug or device because it was unsafe or ineffective. When a phase III trial is completed, the researchers examine the data and decide whether the results have medical importance.

Results from clinical trials are often published in peer-reviewed scientific journals. Peer review is a process by which experts review the report before it is published to ensure that the analysis and conclusions are sound. If the results are particularly important, they may be featured in news media and discussed at scientific meetings and by patient advocacy groups before they are published. Once a new approach has been proven safe and effective in a clinical trial, it may become the standard of medical practice.

Ask the research team members if the study results have been or will be published. Published study results are also available by searching for the study's official name or Protocol ID number in the National Library of Medicine's PubMed® database.

Only through clinical research can we gain insights and answers about the safety and effectiveness of drugs and therapies. Groundbreaking scientific advances in the present and the past were possible only because of participation of volunteers, both healthy and those diagnosed with an illness, in clinical research. Clinical research requires complex and rigorous testing in collaboration with communities that are affected by the disease. As clinical research opens new doors to finding ways to diagnose, prevent, treat, or cure disease and disability, clinical trial participation of volunteers is essential to help us find the answers.

Source: National Institutes of Health. NIH Clinical Trials and You. Available at www.nih.gov. Accessed September 1, 2015